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PMID:20972425

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Citation

Kornberg, MD, Sen, N, Hara, MR, Juluri, KR, Nguyen, JV, Snowman, AM, Law, L, Hester, LD and Snyder, SH (2010) GAPDH mediates nitrosylation of nuclear proteins. Nat. Cell Biol. 12:1094-100

Abstract

S-nitrosylation of proteins by nitric oxide is a major mode of signalling in cells. S-nitrosylation can mediate the regulation of a range of proteins, including prominent nuclear proteins, such as HDAC2 (ref. 2) and PARP1 (ref. 3). The high reactivity of the nitric oxide group with protein thiols, but the selective nature of nitrosylation within the cell, implies the existence of targeting mechanisms. Specificity of nitric oxide signalling is often achieved by the binding of nitric oxide synthase (NOS) to target proteins, either directly or through scaffolding proteins such as PSD-95 (ref. 5) and CAPON. As the three principal isoforms of NOS--neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS)--are primarily non-nuclear, the mechanisms by which nuclear proteins are selectively nitrosylated have been elusive. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is physiologically nitrosylated at its Cys 150 residue. Nitrosylated GAPDH (SNO-GAPDH) binds to Siah1, which possesses a nuclear localization signal, and is transported to the nucleus. Here, we show that SNO-GAPDH physiologically transnitrosylates nuclear proteins, including the deacetylating enzyme sirtuin-1 (SIRT1), histone deacetylase-2 (HDAC2) and DNA-activated protein kinase (DNA-PK). Our findings reveal a novel mechanism for targeted nitrosylation of nuclear proteins and suggest that protein-protein transfer of nitric oxide groups may be a general mechanism in cellular signal transduction.

Links

PubMed PMC2972384 Online version:10.1038/ncb2114

Keywords

Cells, Cultured; DNA-Activated Protein Kinase/metabolism; Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism; Histone Deacetylase 2/metabolism; Humans; Nitric Oxide/metabolism; Nitric Oxide Donors/pharmacology; Nuclear Proteins/metabolism; Signal Transduction; Sirtuin 1/antagonists & inhibitors; Sirtuin 1/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:G3P

enables

GO:0035605: peptidyl-cysteine S-nitrosylase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:G3P

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:G3P

involved_in

GO:0035606: peptidyl-cysteine S-trans-nitrosylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:G3P

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P70288

F

Seeded From UniProt

complete

RAT:G3P

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P97313

F

Seeded From UniProt

complete

RAT:G3P

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q923E4

F

Seeded From UniProt

complete

MOUSE:PRKDC

enables

GO:0019899: enzyme binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P04797

F

Seeded From UniProt

complete

MOUSE:SIRT1

enables

GO:0046969: NAD-dependent histone deacetylase activity (H3-K9 specific)

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:SIRT1

involved_in

GO:0016575: histone deacetylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SIRT1

enables

GO:0019899: enzyme binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P04797

F

Seeded From UniProt

complete

MOUSE:HDAC2

enables

GO:0019899: enzyme binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P04797

F

Seeded From UniProt

complete

MOUSE:SIR1

involved_in

GO:0016575: histone deacetylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SIR1

enables

GO:0019899: enzyme binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P04797

F

Seeded From UniProt

complete

MOUSE:SIR1

enables

GO:0046969: NAD-dependent histone deacetylase activity (H3-K9 specific)

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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